[1]杨 蕤,万生芳,张 磊,等.基于单细胞转录组测序数据识别糖尿病肾病发生发展的关键细胞[J].医学信息,2023,36(20):1-9.[doi:10.3969/j.issn.1006-1959.2023.20.001]
　YANG Rui,WAN Sheng-fang,ZHANG Lei,et al.Identification of Key Cells in the Development of Diabetic Nephropathy Based on Single-cell Transcriptome Sequencing Data[J].Journal of Medical Information,2023,36(20):1-9.[doi:10.3969/j.issn.1006-1959.2023.20.001]
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基于单细胞转录组测序数据识别糖尿病肾病发生发展的关键细胞()
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医学信息[ISSN:1006-1959/CN:61-1278/R]

卷:
36卷
期数:
2023年20期
页码:
1-9
栏目:
生物信息学
出版日期:
2023-10-15

文章信息/Info

Title:
Identification of Key Cells in the Development of Diabetic Nephropathy Based on Single-cell Transcriptome Sequencing Data
文章编号:
1006-1959（2023）20-0001-09
作者:
杨 蕤; 万生芳; 张 磊; 等
（1.甘肃中医药大学基础医学院，甘肃 兰州 730000；2.甘肃省中医方药挖掘与创新转化重点实验室，甘肃 兰州 730000）
Author(s):
YANG Rui; WAN Sheng-fang; ZHANG Lei; et al.
(1.College of Basic Medicine,Gansu University of Traditional Chinese Medicine,Lanzhou 730000,Gansu,China;2.Key Laboratory of Chinese Herbs and Prescription Mining and Innovation and Transformation in Gansu Province,Lanzhou 730000,Gansu,China)
关键词:
糖尿病肾病; 单细胞转录组测序; 间质细胞; 巨噬细胞
Keywords:
Diabetic kidney disease; Single-cell transcriptome sequencing; Stromal cell; Macrophagocyte
分类号:
R587.1
DOI:
10.3969/j.issn.1006-1959.2023.20.001
文献标志码:
A
摘要:
目的 通过单细胞转录组学与大样本表型数据分析糖尿病肾病（DKD）患者肾组织中细胞数量变化以及肾小球组织中相关细胞表型变化，分析在DKD疾病发生发展中起关键性作用的细胞与重要生物学功能。方法 通过GEO数据库选取单细胞数据集GSE131882，使用FindClusters功能对细胞进行聚类，并使用marker基因对得到的细胞群体进行细胞类型鉴定。选取GEO数据库中GSE96804作为表型数据，使用R4.2.0版本中Scissor包识别DKD发病正相关的细胞亚群，筛选关键细胞后绘制差异基因表达火山图，随后对DKD发生发展过程中关键细胞的基因表达进行GSEA富集，并将结果可视化后进行分析。结果 结合单细胞类型鉴定与Scissor结果得出，DKD患者巨噬细胞和间充质细胞、肾β-闰细胞、肾毛细血管内皮细胞、成纤维细胞4种间质细胞Scissor+细胞比例明显高于Scissor-细胞，且细胞数量变化较大；关键细胞通过GSEA分析得出，差异基因主要富集在Toll样受体信号通路、氧化磷酸化信号通路、黏着斑信号通路、ECM受体相互作用信号通路等。结论 肾小球中间充质细胞、肾β-闰细胞、肾毛细血管内皮细胞、成纤维细胞4种间质细胞以及巨噬细胞可能是导致DKD发生发展的关键原因，炎症、能量代谢等功能可能是影响DKD的重要功能。
Abstract:
Objective To analyze the changes of cell number in renal tissue and related cell phenotype in glomerular tissue of patients with diabetic kidney disease (DKD) by single cell transcriptomics and large sample phenotypic data, and to analyze the cells and important biological functions that play a key role in the occurrence and development of DKD disease.Methods The single-cell data set named GSE131882 was chosen from the GEO database, and the cells were then clustered using the FindClusters function. The resulting cell population’s cell types were then determined using marker genes. The phenotypic data named GSE96804 was chosen from the GEO database, and the Scissor program in the R4.2.0 version was used to identify cell subsets that were positively connected to the pathogenesis of DKD. After screening the key cells, the volcano map of differential gene expression was plotted, then the gene expression of key cells in the development of DKD was enriched by GSEA, and the results were visualized and analyzed.Results When single cell type identification was combined with Scissor results, it was discovered that the proportion of Scissor+ cells, which included macrophagocyte, mesenchymal cells, kidney beta-intercalated cells, kidney capillary endothelial cells, and fibroblasts, was significantly higher in DKD patients than that of Scissor- cells. Key cell GSEA analysis revealed that the differential genes were predominantly enriched in the signaling pathways for Toll-like receptors, oxidative phosphorylation, focal adhesion, and ECM-receptor interaction, among other signaling pathways.Conclusion The primary causes of the occurrence and progression of DKD may be attributed to four different types of stromal cells in the glomerulus, including mesenchymal cells, kidney beta-intercalated cells, kidney capillary endothelial cells, fibroblasts, and macrophagocyte. Functions such as energy metabolism, inflammation, and others may have a significant impact on DKD.

参考文献/References:

[1]中华医学会糖尿病学分会微血管并发症学组.中国糖尿病肾脏病防治指南(2021年版)[J].中华糖尿病杂志,2021,13(8):762-784.[2]Magee C,Grieve DJ,Watson CJ,et al.Diabetic Nephropathy: a Tangled Web to Unweave[J].Cardiovasc Drugs Ther,2017,31(5-6):579-592.[3]Tang SCW,Yiu WH.Innate immunity in diabetic kidney disease.[J].Nat Rev Nephrol,2020,16(4):206-222.[4]周志锋,况煌,万智凯,等.天然免疫细胞与糖尿病肾脏疾病[J].中国糖尿病杂志,2020,28(12):955-958.[5]Tesch GH.Diabetic nephropathy-is this an immune disorder?[J].Clin Sci (Lond),2017,131(16):2183-2199.[6]Chow F,Ozols E,Nikolic-Paterson DJ,et al.Macrophages in mouse type 2 diabetic nephropathy:correlation with diabetic state and progressive renal injury[J].Kidney Int,2004,65(1):116-128.[7]聂振勇,赵晶,孙璇君,等.糖尿病肾病患者肾脏巨噬细胞Bruton酪氨酸激酶激活与肾功能的相关性研究[J].安徽医科大学学报,2021,56(12):1897-1903.[8]You H,Gao T,Cooper TK,et al.Macrophages directly mediate diabetic renal injury[J].Am J Physiol Renal Physiol,2013,305(12):1719-1727.[9]Wang Y,Chen X,Cao W,et al.Plasticity of mesenchymal stem cells in immunomodulation:pathological and therapeutic implications[J].Nat Immunol,2014,15(11):1009-1016.[10]王书韵,谢君辉,余学锋.间充质干细胞治疗糖尿病肾病的作用与机制[J].中国组织工程研究,2022,26(1):148-152.[11]Islam MN,Griffin TP,Sander E,et al.Human mesenchymal stromal cells broadly modulate high glucose-induced inflammatory responses of renal proximal tubular cell monolayers[J].Stem Cell Res Ther,2019,10(1):329.[12]张颖超,米焱,王彩丽,等.间充质干细胞治疗糖尿病肾病[J].肾脏病与透析肾移植杂志,2019,28(5):460-464.[13]Zhang L,Li K,Liu X,et al.Repeated systemic administration of human adipose-derived stem cells attenuates overt diabetic nephropathy in rats[J].Stem Cells Dev,2013,22(23):3074-3086.[14]王迪生,孔刘莎,王佳,等.红细胞生成素预处理脂肪间充质干细胞移植治疗大鼠糖尿病肾病[J].中国组织工程研究,2019,23(9):1370-1376.[15]王君仪,陈柯宇,孙明坤,等.脂肪间充质干细胞外泌体在糖尿病肾病中的保护作用及其机制[J].生命的化学,2021,41(10):2111-2118.[16]Yuan S,Liu X,Zhu X,et al.The Role of TLR4 on PGC-1alpha-Mediated Oxidative Stress in Tubular Cell in Diabetic Kidney Disease[J].Oxid Med Cell Longev,2018,2018:6296802.[17]Panchapakesan U,Pollock C.The role of toll-like receptors in diabetic kidney disease[J].Curr Opin Nephrol Hypertens,2018,27(1):30-34.[18]靳贺超,强家维,张冠文,等.当归补血汤通过改善足细胞线粒体功能障碍减轻糖尿病肾病大鼠氧化应激及炎症反应[J].中国实验方剂学杂志,2022,28(3):31-40.[19]Naito Y,Uchiyama K,Handa O,et al.Therapeutic Potential of Astaxanthin in Diabetic Kidney Disease[J].Adv Exp Med Biol,2021,1261:239-248.[20]Ishii T,Furuya F,Takahashi K,et al.Angiopoietin-Like Protein 2 Promotes the Progression of Diabetic Kidney Disease[J].J Clin Endocrinol Metab,2019,104(1):172-180.[21]Ma H,Togawa A,Soda K,et al.Inhibition of podocyte FAK protects against proteinuria and foot process effacement[J].J Am Soc Nephrol,2010,21(7):1145-1156.[22]何东元,郑志贵,陈宜方,等.黄芪甲苷抑制粘着斑激酶磷酸化改善高糖环境下的足细胞黏附能力的研究[J].浙江医学,2019,41(5):414-418.

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更新日期/Last Update: 1900-01-01